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Biomedical subjects

T Shirasaka

Publications and source records attributed to T Shirasaka.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Conceptual changes in cancer chemotherapy--biochemical modulation of 5-FU].

Recently, the demand for more useful therapies for cancer patients has increased. We describe in this paper a therapeutic modality based on a self-rescuing concept (SRC), and which features dual activity, i.e., an effect-enhancing activity and an adverse reaction-reducing activity. We present the theory and practice of S-1, a novel oral fluoropyrimidine anticancer agent designed to enhance anticancer activity and reduce gastrointestinal toxicity through the deliberate combination of the following components: the oral fluoropyrimidine agent tegafur; a DPD inhibitor (CDHP) which is more potent than uracil, which is used in UFT; and an ORTC inhibitor (Oxo) which localizes in the gastrointestinal tract. S-1 is a combination drug with a molar ratio of 1:0.4:1 in FT, CDHP, and Oxo, respectively. A clinical pharmacology study was conducted to examine blood concentrations of 5-FU after twice-a-day administration of S-1 at a dose of 40 mg/m2. Blood concentrations of 5-FU were found to be 60 to 200 ng/ml in all twelve patients examined. The overall response rate was 44.6% (45/101). In addition, the incidence of adverse reactions judged to be grade 3 or higher was 10% or less. We have also reported a combination therapy with 5-FU (civ) (5-FU: 250 to 350 mg/body, 24-hour cvi, consecutive days) and low-dose cisplatin (CDDP: 3 to 5 mg/body, i.v., 5 days/week), in which CDDP was used as a modulator of 5-FU. Low-dose FP therapy provided response rates as high as 40 to 60% in 163 patients with various gastrointestinal cancers other than pancreas cancer. The incidence of the adverse reactions of nausea and vomiting which were judged to be grade 3 or higher was 2.5% (4/163). The incidences of other adverse reactions were 1% or less. In line with the theory and practice of combination therapy with 5-FU (cvi) 24 hr cvi; 5-FU: 750 to 1,000 mg/body/day on Monday, Wednesday, and Friday (withdrawal on Tuesday, Thursday, Saturday and Sunday) intermittent administration and low-dose CDDP (3 to 5 mg/body/day day 1-5/w) consecutive administration was utilized in which there was a difference in cell cycle between gastrointestinal mucosal cell and tumor cell, or between bone marrow cell and tumor cell. Few adverse reactions, e.g., diarrhea and stomatitis, were observed despite the overall response rate being as high as 52.4% (22/42). The incidence of adverse reaction judged to be grade 3 or higher was as low as 9.3% (5/54), with an incidence of 9.3% (5/54) in Grade 3 or higher myelotoxicity. We intend in the future to combine the abovementioned therapeutic modalities, which provoke fewer adverse reactions and are easy on patients with cancer in an effort to further increase their life expectancy.

Administration, Oral↗
PubMed1999

Self-Assembly of a Radially Functionalized Hexagonal Molecule: Hexakis(4-hydroxyphenyl)benzene.

Two different porous hydrogen-bonded networks are formed by self-assembly of the radially substituted host 1. In the network of type A, formed by 1 small middle dot4 Et(2)O, all OH groups of 1 are involved in hydrogen bonding, and the molecular sheets are stacked without translation to generate extended channels that accommodate the Et(2)O molecules. Four OH groups of 1 are involved in the type B network of 1 small middle dot4 DMF, and lateral translation of the sheets in an ABAB sequence generates large chambers, each of which contains four DMF molecules.

Journal Article↗
PubMed1999

Quantitative reduction of type I adenylyl cyclase in human alcoholics.

The amounts of adenylyl cyclase type I (AC I) were examined in various parts of the postmortem brains from alcoholics who prior to death had been abstinent from alcohol for at least 6 months and compared with controls using immunoblot analysis with anti-AC I specific antibody. It was revealed that a significant reduction of AC I was observed in both frontal and temporal cortices. On the other hand, in other areas (occipital cortex, caudate nucleus, putamen, and hippocampus) the amounts were comparable between alcoholics and controls. In the next step, we examined two subtypes of human AC mRNA levels (AC I and AC VIII) in blood cells by quantitative RT-PCR using [alpha-32P]dCTP with two sets of the synthetic oligonucleotide primers based on the DNA sequences reported elsewhere (Villacres, E.C. et al., Genomics 16 (1993) 473-478; J. Parma et al., Biochem. Biophys. Res. Commun. 179 (1991) 455-462). The amounts of amplified DNAs of both AC I and AC VIII were significantly smaller in alcoholics than in controls. On the other hand, the amounts of amplified DNA of beta-actin DNA were almost equal between alcoholics and controls. It appears from these results that a reduction in the amount of AC subtypes may be a biological marker for alcoholics.

Adenylyl Cyclases↗
PubMed1999

Participation of arterial baroreceptors input and peripheral vasopressin in the suppression of renal sympathetic nerve activity induced by central salt loading in conscious rats.

We examined whether renal sympathetic nerve activity (RSNA) is suppressed in response to intracerebroventricular (i.c.v.) administration of hypertonic saline (HS) in conscious rats. RSNA was suppressed by i.c.v. administration of HS (0.3 M, 0.67 M, and 1.0 M, 1 microl/min for 20 min) in a concentration-dependent manner, which was attenuated under pentobarbital anesthesia. To elucidate mechanisms responsible for central HS-induced decrease in RSNA, possible involvement of arterial baroreceptors and peripheral arginine vasopressin (AVP) secreted from the posterior pituitary gland was examined using sinoaortic denervated (SAD) rats and non-peptide vasopressin receptor antagonists. The maximum suppression of RSNA (-81.5 +/- 5.5%) in control rats was significantly attenuated to -32.5 +/- 6.7% in SAD rats and to -55.8 +/- 5.7% in rats pretreated with intravenous vasopressin V1 receptor antagonist, OPC-21268 (5 mg/kg, i.v.). However, in SAD rats, pretreatment with vasopressin V1 receptor antagonist did not further affect the RSNA inhibition induced by central salt loading. The results suggest that the suppression of RSNA during central salt loading is mainly dependent on the arterial baroreceptors input and the 'additive' role of peripheral vasopressin.

Animals↗
PubMed1999

Nociceptin modulates renal sympathetic nerve activity through a central action in conscious rats.

Nociceptin, an endogenous agonist of the opioid receptor-like(1) receptor, is expressed in the hypothalamus, where it is implicated in autonomic nervous system control. However, the central actions of nociceptin on sympathetic nerve activity have not been studied. We investigated the effect of intracerebroventricularly administered nociceptin (2-10 nmol) on blood pressure, heart rate (HR), and renal sympathetic nerve activity (RSNA) in conscious rats and sinoaortic-denervated (SAD) rats. Intracerebroventricularly administered nociceptin resulted in a dose-dependent decrease in mean arterial pressure (MAP) and HR in intact rats. RSNA decreased 31.5 +/- 2.1 and 19.9 +/- 5.0% at a dose of 2 and 5 nmol, respectively. In SAD rats, MAP, HR, and RSNA decreased in a dose-dependent manner, and the maximum responses were larger than those in intact rats. The decrease in HR induced by nociceptin was blocked by propranolol but not by atropine, which indicates that nociceptin is acting by inhibiting cardiac sympathetic outflow. These nociceptin-induced depressor and bradycardic responses were not antagonized by pretreatment with naloxone and nocistatin. These findings suggest that central nociceptin may have a functional role in regulating cardiovascular and sympathetic nervous systems.

Animals↗
PubMed1999

Sympathetic and cardiovascular actions of orexins in conscious rats.

The novel hypothalamic peptides orexin-A and orexin-B are known to induce feeding behavior when administered intracerebroventricularly, but little is known about other physiological functions. The renal sympathetic nerves play important roles in the homeostasis of body fluids and the circulatory system. We examined the effects of intracerebroventricularly administered orexins on mean arterial pressure (MAP), heart rate (HR), renal sympathetic nerve activity (RSNA), and plasma catecholamine in conscious rats. Orexin-A (0.3, 3. 0 nmol) provoked an increase in MAP (94.3 +/- 0.7 to 101.9 +/- 0.7 mmHg and 93.1 +/- 1.1 to 108.3 +/- 0.8 mmHg, respectively) and RSNA (28.0 +/- 7.0 and 57.9 +/- 12.3%, respectively). Similarly, orexin-B (0.3, 3.0 nmol) increased MAP (93.9 +/- 0.9 to 97.9 +/- 0.9 mmHg and 94.5 +/- 1.1 to 105.3 +/- 1.7 mmHg, respectively). Orexin-A and -B at 3.0 nmol also increased HR. In other conscious rats, a high dose of orexin-A and -B increased plasma norepinephrine. Plasma epinephrine only increased with a high dose of orexin-A. These results indicate that central orexins regulate sympathetic nerve activity and affect cardiovascular functions.

Animals↗
PubMed1999

Synthesis of the optical isomers of 4-[1-(4-tert-butylphenyl)-2-oxo- pyrrolidine-4-yl]methyloxybenzoic acid (S-2) and their biological evaluation as antilipidemic agent.

The enantiomers of (+/-)-4-[1-(4-tert-butylphenyl)-2-oxo-pyrrolidine- 4-yl]methyloxybenzoic acid (S-2), a new antilipidemic agent having dual action on the plasma triglyceride (TG) and cholesterol (Cho) lowering effects, were prepared via separation by Chiralcel OJ column chromatography of their methyl ester and also by the same method as the described racemate's synthesis from optically active 1-(4-tert-butylphenyl)-2-oxo-pyrrolidine-4-carboxylic acid respectively. These optically active carboxylic acids were prepared by the resolution of diastereomeric N-[(S)-(-)-[4-methyl-(alpha-methyl)benzyl]]-1-(4-tert-butylphenyl)-2-oxo - pyrrolidine-4-carboxyamide using silica gel column chromatography, followed by deamination with N2O4. The absolute configurations for the enantiomers of S-2 were indirectly determined using X-ray analysis of the 4-bromo-2-fluorobenzamide of the (+)-4-[1-(4-tert-butylphenyl)-2- oxo-pyrrolidine-4-yl]-methyloxybenzoic acid. S-2 and its enantiomers showed an essentially equipotent activity on the fatty acid- and sterol-biosynthesis inhibition in vitro. On the other hand, in the in vivo activity, (S)-(+)-4-[1-(4-tert-butylphenyl)-2-oxo-pyrrolidine- 4-yl]methyloxybenzoic acid (S-2E) was superior in the lowering abilities of the plasma TG and phospholipid(PL) and was chosen as a candidate for a novel antilipidemic agent. The difference in the in vivo activity among S-2 and its enantiomers was explained from the pharmacokinetics after administration p.o.

Benzoates↗
PubMed1999

Persistent induction of apoptosis and suppression of mitosis as the basis for curative therapy with S-1, an oral 5-fluorouracil prodrug in a colorectal tumor model.

In an effort to improve the therapeutic selectivity of 5-fluorouracil (FUra) against colorectal cancer, S-1, a combination agent including a prodrug of FUra with two modulators, was recently developed by Taiho Pharmaceuticals Co. S-1 is a combination of tegafur (FT), 5-chloro-2,4-hydroxypyridine, and potassium oxonate in the molar ratio of 1.0:0.4:1.0, with the latter two components as inhibitors of dihydropyrimidine dehydrogenase and phosphoribosylpyrophosphate transferase, respectively. In this study, the therapeutic selectivity and efficacy of S-1 (oral) was compared with FT (oral) and FUra (i.v. infusion) in rats bearing advanced colorectal cancer by using clinically relevant schedules. The maximum tolerated doses (MTDs) of S-1, FT, and FUra were 31.5, 200, and 25 mg/kg/d for 7 days and 22.5, 150, and 12.5 mg/kg/d for 28 days, respectively. The therapeutic index of S-1 was 4- to 5-fold higher than that of either FT or FUra. S-1 achieved 100% complete tumor regression (CR) at its MTD in both 7-day and 28-day schedules. Furthermore, the high incidences of stomatitis, alopecia, and diarrhea observed with FUra and FT, were not observed with S-1. In an attempt to understand the basis for the observed superior therapeutic selectivity with S-1, we studied pharmacokinetic analysis of FUra, drug-induced apoptosis, suppression of mitosis, and inhibition of thymidylate synthase (TS) after S-1, FUra, or FT administration. The peak plasma FUra concentrations derived from FUra or S-1 (FT) at comparable MTDs were similar, but the plasma level of FUra was higher with S-1 than with FUra. Induction of high and sustained apoptosis was achieved with S-1. Although the initial level of apoptosis induced by FUra was comparable to S-1, it was not sustained. The sustained level of apoptosis appears to correlate with tumor growth inhibition. Mitotic figures were more greatly suppressed with S-1 treatment than with FUra. Studies on TS inhibition indicated that, although both S-1 and FUra caused a 4- to 6-fold induction of total TS protein, single oral administration of S-1 was superior to 24-h infusion of FUra in suppressing free TS. The data are consistent with the observation that the therapeutic efficacy of S-1 (100% cure) over FUra is associated with high and sustained levels of drug-induced apoptosis, greater suppression of mitosis, and inhibition of free TS in tumor tissues.

Animals↗
PubMed1999

[Combination therapy of continuous venous infusion (CVI) of 5-FU and low dose consecutive cisplatin (CDDP), and the new oral anti-cancer drug S-1 for advanced gastro-intestinal cancer].

Highly effective treatment is required for patients with advanced GI cancer. Returning to the starting point for reconsideration of cancer chemotherapy, with the aim of attaining a therapy (self rescuing concept: SRC) with more potential efficacy and less toxicity than current therapy, we report two kinds of chemotherapy in the present paper. They were set up preclinically using the theory of 5-FU biochemical modulation, and demonstrated their usefulness in clinical practice. S-1 is a newly developed oral anti-cancer drug which is a combination of Tegafur (FT), a prodrug of 5-FU and two modulators (CDHP, an inhibitor of 5-FU degradation and Oxo, a selective inhibitor GI toxicity by 5-FU) at a molar ratio of 1:0.4:1. In combination with CDHP, 5-FU gradually released from FT remained longer in plasma, and consequently had high anti-tumor activity, while the combined Oxo significantly suppressed GI toxicity due to 5-FU. The response rate to S-1 of stomach cancer in a phase II study was 46.5% (60/129). Toxicity at more than G3 was less than 10%. In the combination therapy employing 5-FU by CVI (5-FU: 250-350 mg/body for 24 h, 4-6 wks) and low dose consecutive CDDP, CDDP acts mainly as a modulator of 5-FU (to increase 5-FU sensitivity for tumor by inhibition of intracellular Met incorporation). For this purpose, it was found that daily consecutive administration is required, even at low dose of CDDP (3-5 mg/body/day for 5 days). A high response rate (40-60%) was obtained for advanced GI cancer. Toxicity at more than G3 was less than 10%. On the other hand, the possibility has been suggested that so far as 5-FU is concerned, CVI every other day (500-750 mg/body/day for 3 days) is more favorable than long term CVI, with regard to decreasing GI and myelotoxicities based upon the difference in generation time between normal cell (GI mucous membrane and stem cell) and tumor cell cycles. The possibility is suggested that the above-mentioned chemotherapy can become a standard therapy for GI cancer.

Administration, Oral↗
PubMed1999

[Biochemical modulation of 5-FU--effect of low dose CDDP].

A pilot study of continuous or intermittent low dose 5-FU and cisplatin chemotherapy (low-dose FP therapy) was conducted at the Department of Surgery of Sapporo Medical University School of Medicine (Group A) and Sapporo Tsukisamu Hospital, and at the Department of Internal Medicine of the Kochi Prefectural Center Hospital (Group B). The cases with esophageal cancer, stomach cancer, pancreatic cancer, hepatocellular carcinoma or colonic cancer co-existing with their inoperable lesion(s) were considered in this chemotherapy. The rates of complete and partial response and of side effects were studied. Also, the effects of low-dose FP on the prognosis of the patients with pancreatic or colonic cancers were investigated. The procedure consisted of continuous 5-FU 320 mg/m2 i.v. with daily CDDP 2.5 mg/m2 i.v. for five days/week rescue was performed for at least four weeks as a rule. The rates of complete response and partial response were 64% (Group A) and 56% (Group B) in esophageal cancer, 62% (Group A and B) in stomach cancer, 48% (Group A) and 57% (Group B) in colonic cancer, and 8% (Group A) and 21% (Group B). The overall response rate was 57.8%. The frequencies of severe side effect(s) (grades 3 and 4) were within three to eight percent, and no death from side effect(s) was experienced. The effects of low-dose FP therapy on the prognosis of stage IV colonic cancer and stage IV b pancreatic cancer were studied retrospectively. It is suggested that this chemotherapy might contribute to the survival of patients with these two cancers. Otherwise, the chemotherapy of intermittent administration (day by day) of 5-FU 750 mg/m2 i.v. and CDDP 2.5 mg/m2 i.v. was selected in order to decrease the rate of side effects and their severity. The pilot study encountered no severe side effects, no cases with grade 4 side effect were experienced but the remission rates were mostly similar to that of sequential low-dose FP therapy. However, the side effect of low grade ones as symptoms in gastrointestinal tract were observed in more patients. We concluded that sequential or intermittent 5-FU/CDDP therapy might be fairly effective, and since the adjuvant chemotherapy of choice for advanced or recurrent gastrointestinal cancer, their FP therapy might be one of the adjuvant treatments.

Adenocarcinoma↗
PubMed1999

[Chemotherapy with low-dose CDDP and continuous 5-FU for the treatment of advanced gastric cancers].

INTRODUCTION: 5-fluorouracil (5-FU) has been widely used for the treatment of gastrointestinal cancers. On the basis of recent findings, low-dose Cisplatin (CDDP) and continuous venous infusion of 5-FU have shown additive or synergistic antitumor effects in experimental models. We evaluated clinical effects of low-dose CDDP and 5-FU (low-dose FP therapy) in patients with advanced gastric cancers. PATIENTS AND METHODS: In December 1993 and June 1998, 52 patients with advanced gastric cancer were entered in this study. Patients were considered eligible if they had a bidimensionally measurable tumor. 5-FU (160 mg/m2/day) was continuously infused over 24 hours using an implantable port, and CDDP (3 mg/m2/day) was infused for half an hour. The administration schedule consisted of 5-FU for 7 consecutive days and CDDP for 5 days followed by a 2-day rest every four weeks according to response and tolerance. RESULTS: Low-dose FP therapy was given 44 patients (85%). The response rate was 65.9% and median survival time was 249 days. The responder group showed good survival compared with the non-responder group. The regimen was tolerable, and the most common toxicity was anorexia (40.3%). Three patients suffered from grade 3 anorexia, leukopenia and mucositis. On the other hand, renal dysfunction occurred in 50% (two of four patients administered over 1,000 mg CDDP). These results raise the possibility that the dose-limiting factor of low-dose FP therapy may account for the total dosage of CDDP. CONCLUSION: Low-dose FP therapy promises to be effective in the clinical management of advanced gastric cancer.

Adenocarcinoma↗
PubMed1999

Pharmacokinetic study of S-1, a novel oral fluorouracil antitumor drug.

S-1 is a novel oral fluorouracil antitumor drug that combines three pharmacological agents: tegafur (FT), which is a prodrug of 5-fluorouracil (5-FU); 5-chloro-2,4-dihydroxypyridine (CDHP), which inhibits dihydropyrimidine dehydrogenase (DPD) activity; and potassium oxonate (Oxo), which reduces gastrointestinal toxicity. Phase I and early Phase II clinical trials have already been completed. On the basis of the results of these trials, 80 mg/m2/day, given daily in two divided doses after breakfast and supper, a 28-day consecutive oral regimen is recommended. In this study, we investigated the pharmacokinetics of 5-FU, intact FT, CDHP, and Oxo, after administration of S-1, at a standard dose of 80 mg/m2/day, in advanced cancer patients. Twelve patients were recruited to the study; 5 patients with gastric cancer, 4 with colorectal cancer, and 3 with breast cancer. Among them, analysis was conducted on 12 patients for single administration and on 10 patients for consecutive administration. The initial dose of S-1 for each patient was determined according to his/her body surface area (BSA) as follows: for BSA < 1.25 m2, 80 mg/body/day; for 1.25 m2 < or = BSA < 1.5 m2, 100 mg/day; and for 1.5 m2 < or = BSA, 120 mg/day. For single administration, half of the standard dose was used. For 28-day consecutive administration, the standard dose was given daily in two divided doses. The average single dose per BSA was 35.9 mg/m2 (31.7-39.7 mg/m2). Pharmacokinetic parameters of plasma 5-FU were as follows: Cmax, 128.5 +/- 41.5 ng/ml; Tmax, 3.5 +/- 1.7 h; AUC(0-14), 723.9 +/- 272.7 ng x h/ml; and T(1/2), 1.9 +/- 0.4 h. In the 28-day consecutive regimen, there were no fluctuations in pharmacokinetics nor any drug accumulation. Because the pharmacokinetics of orally administered S-1 is almost similar to that of continuous i.v. infusion of 5-FU, we concluded that S-1 may improve patients' quality of life.

Adult↗
PubMed1999

Low-dose cisplatin and 5-fluorouracil in combination can repress increased gene expression of cellular resistance determinants to themselves.

The synergistic mechanism of cisplatin (CDDP) and 5-fluorouracil (5-FU) in combination remains unclear, despite its substantial antitumor activity, which has been demonstrated clinically. To clarify the mechanism(s), we determined the sensitivity or resistance factors to either drug in seven gastrointestinal cancer cell lines and then analyzed the altered gene expression after different exposures to CDDP and 5-FU. At the basal gene expression level, glutathione S-transferase pi (GSTpi) expression correlated with the observed resistance to CDDP, whereas dihydropyrimidine dehydrogenase (DPD) and multidrug resistance-associated protein (MRP) expression was related to 5-FU resistance. GSTpi, DPD, and MRP expression increased in response to the respective drug, but they also increased in response to the other drug as well. Additionally, 5-FU revealed a drastically increased thymidylate synthase (TS) gene expression in 5-FU-resistant cells. However, the increasing actions of CDDP and 5-FU on GSTpi, DPD, MRP, and TS expression varied according to the exposure time, concentration, and schedule. A low concentration of CDDP (1 microg/ml, 30 min) followed by 5-FU (0.5 microg/ml, 72 h) was found to cause a less increased expression of DPD, MRP, GSTpi, and TS than either drug alone, thus resulting in synergistic cytotoxicity in 5-FU-resistant COLO201 and CDDP-resistant HCC-48 cells. The sequential combination of CDDP and 5-FU inhibited the growth of human normal renal proximal tubule cells by less than 20%. Low concentrations of CDDP followed by continuous exposure to 5-FU can repress increased gene expression related to both drug resistances, thereby being synergistically cytotoxic in human gastrointestinal cancer cells.

ATP-Binding Cassette Transporters↗
PubMed1999

[Low-dose FP therapy for advanced and recurrent gastric cancer].

Continuous infusion of 5-FU and low-dose CDDP infusion (low-dose FP therapy) is one of the effective combination chemotherapies for advanced and recurrent gastric cancer. Several studies have reported low-dose FP therapy showed high response rates (40-50%) and a low incidence of toxicities. There was a positive correlation between antitumor effect and survival time on neoadjuvant chemotherapy for advanced gastric cancer. It still may be necessary to improve quality of life by changing the regimen of low-dose FP therapy because patients require hospitalization for the therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

[Combination chemotherapy of continuous infusion 5-FU and daily low-dose CDDP in colorectal carcinoma].

Continuous intravenous infusion (CVI) of 5-fluorouracil (5-FU) plus daily low-dose cisplatin (CDDP) was evaluated in 59 patients with advanced and unresectable colorectal carcinoma. The procedure consisted of 5-FU 320 mg/m2/day, CVI and CDDP 2.5-3.5 mg/m2/day, infused for one hour five times a week (low-dose FP therapy) was performed for at least four weeks. The rates of complete and partial response, along with side effects were studied. Also, the effect of low-dose FP therapy on the prognosis of patients with colorectal carcinoma was investigated. The rate of complete and partial response was 57.1%. The frequency of severe side effects (grade 3 and 4) was 10.5%, and no death from side effects was noted. The effect of low-dose FP therapy on the prognosis of advanced and unresectable colorectal carcinoma was studied. It is suggested that this chemotherapy might contribute to the survival of patients with colorectal carcinoma. We designed the chemotherapy of intermittent administration (day by day) of 5-FU 600 mg/m2/day and daily CDDP 2.5-3.5 mg/m2/day (intermittent FP) in order to decrease the rate of side effects and their severity. No cases with grade 3 or 4 side effects were experienced, but the response rate was mostly similar to that of low-dose FP therapy. We concluded that low-dose FP and intermittent FP therapy might be fairly effective for advanced and unresectable colorectal carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

[Ambulatory and domiciliary cancer chemotherapy with forearm implant catheter system and low-dose CDDP + 5-FU therapy].

Shortening the period of hospitalizations and improving QOL attracting a great deal of attention in the field of medicine recently. Therefore, ambulatory and domiciliary treatment has become more important. This is not an exception in cancer therapy; the conversion from hospital treatment to ambulatory and domiciliary treatment is promoted. However, there is the danger of a lowered QOL as a resistant side effect, when the conventional cancer chemotherapy in the hospital is used as the ambulatory and domiciliary treatment. Recently, low-dose CDDP + 5-FU therapy (LFP therapy) that applies biochemical modulation has been developed for advanced gastrointestinal cancers. This therapy is thought to have a good antitumor effect and slight side effects, so it can be widely used. However, this therapy needs the continuous injection of 5-FU, so the hospital treatment was necessary, and ambulatory treatment was difficult with the usual administration method. Thus, we implanted a forearm central venous catheter system (forearm IVH reservoir), through which we can administer medication safely and conveniently without limiting the patient activity. LFP therapy was attempted in ambulatory and domiciliary treatment. Low-dose FP therapy consisted of 5-FU (160 mg/m2/day every day by continuous infusion) and cisplatin (3 mg/m2/day in 100 ml of normal saline by infusion over 30 minutes on days 1-5/W). Patients were treated for 4 consecutive weeks with a subsequent one-week rest period. The overall response rate was 52.1%. Grade 3 toxicity was observed in 5% of patients. An advantage was that in the ambulatory and domiciliary cancer chemotherapy the hematotoxicity was slight, and LFP therapy could be continued safely. In addition, it was also possible to attempt the improvement in QOL with the forearm IVH reservoir system. LFP therapy using the forearm IVH reservoir system may develop as a standard method of ambulatory and domiciliary cancer chemotherapy in the future.

Adult↗
PubMed1998

Biochemical modulation therapy for pancreatic cancer.

It is well known that the clinical course in most patients with advanced pancreatic cancer is not influenced substantially by chemotherapy and/or radiotherapy. However, new chemotherapy, based on the synergistic antitumor activities of 5-fluorouracil (5-FU) and cisplatin (CDDP) producing biochemical modulation in solid cancers diagnosed as adenocarcinoma, has recently been reported to be effective. In gastrointestinal cancers, the optimal concentrations of each drug and the duration of the anticancer effects, as well as adverse effects have been confirmed in pharmacodynamic studies. Our experience of this treatment for advanced pancreatic cancer (stage IV) indicates the usefulness of the antitumor effect in terms of both effect on the tumor size in unresectable patients and prognosis in resectable patients. These results were remarkable in patients diagnosed as stage IV b and/or curability C. Although there were adverse effects, none were severe. However, anything compromising the patient's quality of life must be prevented. Randomized prospective studies of the combination of 5-FU and CDDP are expected in the near future.

Adenocarcinoma↗